Natural genetic sequence variability exists between individuals in any and every population. Subtle alteration(s) in the primary nucleotide sequence of a gene encoding a pharmaceutically-important protein may be manifested as significant variation in expression, structure and/or function of the protein. Such alterations may explain the different response of individuals to therapy with a particular drug.
Variability in genetic sequence is particularly likely to cause a variable response to therapy when the therapeutic is an antisense compound that modulates the expression of protein through specific hybridization to the genetic sequence. In this case, changes in the sequence of the DNA or RNA can have a direct effect on the ability of such a compound to specifically hybridize.
Identification of polymorphisms among various populations is desirable to tailor design of suitable antisense therapeutics, select antisense therapeutics to administer to a particular population, and also predict responsiveness to therapeutics.